Search

[Background] Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients., [Methods] We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a metaanalysis of both case-control panels., [Results] We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P, [Conclusions] We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid19 pathophysiology., The IKMB's core facilities received infrastructure support by the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI, EXC2167). The project also received support through a philanthropic donation by Stein Erik Hagen and Canica AS. L.V. was funded by the Fondazione IRCCS Ca’ Granda «COVID-19 Biobank» research grant. This work was also supported by the Ministero dell’Istruzione, dell’Università e della Ricerca – MIUR project "Dipartimenti di Eccellenza 2018 – 2022" (n° D15D18000410001) to the Department of Medical Sciences, University of Torino. The IKMB authors received financial support from the UKSH Foundation "Gutes Tun!" (special thanks to Alexander Eck, Jenspeter Horst and Jens Scholz) and the German Federal Ministry of Education and Research (BMBF; grant ID 01KI20197). HLA-Typing was performed and supported by the Stefan-MorschStiftung. M.A.H was supported by the Spanish Ministry of Science and Innovation ‘JdC fellowship IJC2018-035131-I.

To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity., This study was partly supported by Yara. Analysis of fatty acids was funded by the Spanish MICINN through grant AGL2016-76832-R. The authors acknowledge the financial support by the Land Schleswig-Holstein within the funding program “Open Acesss Publikationsfonds”.

This study aimed to evaluate whether resveratrol (RSV) and its microbial metabolites dihydro-resveratrol (DHR) and lunularin (LUN) affected fatty acid metabolism and omega-3 polyunsaturated fatty acid (n3-PUFA) synthesis in cultured hepatocytes. To this end, cultured human HepG2 hepatocytes were treated with non-toxic concentrations of these polyphenols (40 μM) and Δ5- and Δ6-desaturase (FADS1 and FADS2, respectively) expression was measured. Resveratrol induced both genes but DHR and LUN showed no effect. Co-incubation of RSV with α-linolenic acid (ALA) also induced FADS1 and FADS2 expression. Moreover, transcription of carnitine palmitoyltransferase 1A and fatty acid synthase expression was increased, indicating induction of β-oxidation and fatty acid synthesis, respectively. Using gas chromatography to measure fatty acid levels, we observed the impact of RSV with and without ALA treatment on fatty acid composition. However, RSV reduced unsaturated while increasing saturated fatty acid levels. We found lower amounts of monounsaturated fatty acids (16:1n-7c, 18:1n-9c, 18:1n7c, and 20:1n-9) and n3-PUFA docosahexaenoic acid whereas unsaturated fatty acid levels, especially of stearic acid, were elevated. Of interest, once we co-incubated the cells with RSV together with bovine serum albumin, we found no differences in gene expression compared to cells without RSV treatment. Although we found no positive effect of RSV on n3-PUFA synthesis, the stilbene could possibly prevent cellular stress by decreasing unsaturated fatty acid levels., GK was kindly funded by a fellowship from the Wilhelm Schaumann foundation (Hamburg, Germany). SdP-T was funded by the Spanish MICINN through the grant AGL2016-76832-R., We acknowledge financial support by Land Schleswig-Holstein within the funding programme Open Access Publikations fonds.

On HELENA study group., [Background]: The ideal cardiovascular health (iCVH) construct consists of 4 health behaviours and 3 health factors and is strongly related to later cardiovascular disease. However, the prevalence of iCVH in European adolescents is currently unknown. [Methods]: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study is a cross-sectional, multicentre study conducted in 9 European countries during 2006–2007 and included 3528 adolescents (1683 boys and 1845 girls) between 12.5 and 17.5 years of age. Status (ideal vs. non-ideal) for the health behaviours (smoking status, body mass index, physical activity and diet) and health factors (total cholesterol, blood pressure and fasting glucose) were determined. [Results]: Overall, the prevalence of ideal health behaviours was low; non-smoking (60.9% ideal), body mass index (76.8%), physical activity (62.1%), and diet (1.7%). The prevalence of ideal health factors was; total cholesterol (65.8%), blood pressure (62.0%) and plasma glucose (88.8%). [Conclusions]: The low prevalence of iCVH behaviours, especially diet and physical activity, identified in European adolescents is likely to influence later cardiovascular health which strongly motivates efforts to increase ideal health behaviours in this population., The HELENA project was supported by the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034). The data for this study was gathered under the aegis of the HELENA project, and further analysis was additionally supported by the Spanish Ministry of Economy and Competitiveness (grants RYC-2010-05957 and RYC-2011-09011), the Spanish Ministry of Health: Maternal, Child Health and Development Network (grant RD16/0022), the Fondo Europeo de Desarrollo Regional (MICINN-FEDER) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). Pontus Henriksson was supported by a grant from the Henning and Johan Throne-Holst Foundation. Hanna Henriksson was supported by grants from the Swedish Society of Medicine and the County Council of Östergötland, Sweden.

To produce fish of a high quality that are rich in omega-3 fatty acids (n-3 FA) and simultaneously generate more sustainable aquaculture, the combined use of phytochemicals and vegetable oils in fish feed seems to be a promising approach. Resveratrol (RV) potentially induces endogenous fatty acid synthesis, resulting in elevated n-3 FA levels in fish. RV putatively influences ∆6-desaturase, the key enzyme in FA metabolism, and serves as a ligand for PPARα, a transcription factor regulating β-oxidation. Rainbow trout (36.35 ± 0.03 g) were randomly allocated into six groups and fed diets with reduced fish oil levels (F4 = 4%, F2 = 2% and F0 = 0% of dry matter) supplemented with 0.3% (w/w) RV (F4 + RV, F2 + RV and F0 + RV). RV significantly affected FA composition in liver tissue and whole fish homogenates. 20:5n-3 (EPA) and 22:6n-3 (DHA) were significantly increased whereas precursor FA were diminished in fish fed the F2 + RV and F0 + RV diets when compared to F4 + RV and F0. RV significantly elevated ∆6-desaturase protein levels in the livers of F0 + RV fed animals. Hepatic mRNA expression of ∆6-desaturase, PPARα, and its target genes were affected by the dietary fish oil level and not by dietary RV. The results of this study indicated a potential benefit of supplementing RV in fish oil deprived diets elevating n-3 FA levels in rainbow trout., The study was funded by the DFG-Deutsche Forschungsgemeinschaft (grant numbers: RI 884/8-1; SCHU 2308/4-1). We acknowledge financial support by Land Schleswig-Holstein within the funding programme Open Access Publikationsfonds.